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Effect of Feeding Types on Pathophysiologic Response in Premature Infants and Intestinal Epithelial Cells

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Title: Effect of Feeding Types on Pathophysiologic Response in Premature Infants and Intestinal Epithelial Cells
Author(s): Chen, Yimin
Advisor(s): Fantuzzi, Giamila
Contributor(s): Koh, Timothy; Rao, Mrinalini; Patel, Aloka; Schoeny, Michael; Fantuzzi, Giamila
Department / Program: Kinesiology, Nutrition, and Rehabilitation
Degree Granting Institution: University of Illinois at Chicago
Degree: PhD, Doctor of Philosophy
Genre: Doctoral
Subject(s): Human milk Premature infants Inflammation Oxidative stress Cytotoxicity Necrotizing enterocolitis
Abstract: Human milk (HM) from the infant’s mother is the recommended feeding for premature infants because it contains important bioactive components. Necrotizing enterocolitis (NEC) is a severe inflammatory bowel disease of premature infants characterized by inflammation, oxidative stress, and necrosis. Feeding HM reduces the risk for NEC. Although several bioactive HM components and partial HM fractions alter inflammation in vitro, it is difficult to extrapolate these results to the in vivo situation, since the infant ingests whole HM that subsequently mixes with digestive enzymes. This study had two aims. In Aim 1, we determined oxidative stress (urinary F2-isoprostanes measured by ELISA) and intestinal damage/maturation (urinary Intestinal Fatty Acid Binding Protein (I-FABP) measured by ELISA) in serial urine samples (pre- and post-first feeding, and weekly to 21 days) from 22 premature infants in relation to HM intake over the first 21 days of life. Infants were divided into two feeding groups: HM (HM ≥50% of enteral intake) vs. formula (HM <50%). Our data indicate that after the first feeding, HM-fed infants had a decreased trend in F2-isoprostane levels, whereas urinary I-FABP levels increased significantly in formula-fed infants. F2-isoprostane decreased and I-FABP increased significantly over time in HM-fed infants. In Aim 2 we determined the effect of digested whole HM (n=10 individual samples) on inflammation (interleukin 8; IL-8, measured by ELISA), oxidative stress (F2-isoprostane, by ELISA), and cytotoxicity (released lactate dehydrogenase) in vitro in fully differentiated Caco2 intestinal epithelial cells cultured under conditions that mimic potential insults present in the premature infant’s gastrointestinal tract, i.e., stimulation with the bacterial product lipopolysaccharide (LPS) or the pro-inflammatory cytokine Tumor Necrosis Factor (TNF) – Results indicate that HM significantly suppressed IL-8 and cytotoxicity in TNF-stimulated cells, while also suppressing cell death under baseline conditions. Individual HM samples differed widely in modulating cellular responses. We conclude that HM decreases oxidative stress and inflammation, while reducing cell death in premature infants thus reducing risk for NEC.
Issue Date: 2017-04-20
Type: Thesis
URI: http://hdl.handle.net/10027/21759
Date Available in INDIGO: 2017-10-27
Date Deposited: May 2017
 

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